260-2017-02-13
Rick Gilmore 2017-02-12 11:54:54
Prelude
VIDEO
Today’s Topics
Neurotransmitters
Quiz 2 on Friday.
Review Exam 1 on Friday.
The influx of which ion triggers the release of neurotransmitters from the axon terminal?
The influx of which ion triggers the release of neurotransmitters from the axon terminal?
This type of postsynaptic receptor does NOT contain its own ion channel.
Ionotropic
Metabotropic
Ligand-gated
This type of postsynaptic receptor does NOT contain its own ion channel.
Ionotropic
Metabotropic
Ligand-gated
Neurotransmiters
Amino acids
Glutamate (Glu)
Gamma aminobutyric acid (GABA)
Glycine
Aspartate
Glutamate
Primary excitatory NT in CNS
Role in learning (via NMDA receptor)
Transporters on neurons and glia (astrocytes and oligodendrocytes)
Linked to umami (savory) taste sensation, think monosodium glutamate (MSG)
Dysregulation in schizophrenia? (Javitt 2010)
Glutamate
Ionotropic
AMPA
Na+, K+
Kainate
NMDA
Ca++
Metabotropic
mGlu
GABA
Primary inhibitory NT in CNS
Excitatory in developing CNS, \[Cl-\] in >> \[Cl-\] out
Binding sites for benzodiazepines (e.g., Valium), barbiturates, ethanol, etc.
Ionotropic
GABA-A
Cl-
Metabotropic
GABA-B
K+
Acetylcholine (ACh)
Primary NT of CNS output
Somatic nervous system (neuromuscular junction)
Autonomic nervous system
Sympathetic branch: preganglionic neuron
Parasympathetic branch: pre/postganglionic
Inactivation by acetylcholinesterase (ACh)
Acetylcholine
Ionotropic
Nicotinic (nAChR)
Na+, K+
e.g., Curare
Metabotropic
Muscarinic (mAChR)
K+
e.g., Atropine
How to stop your prey
Japanese pufferfish toxin
Blocks voltage-gated Na+ channels
Black widow spider venom
Accelerates presynaptic ACh release
Botulinum toxin
Prevents ACh vesicles from binding presynaptically
Sarin nerve gas
Impedes ACh breakdown by AChE
Pesticides
Impede AChE
Tetanus toxin
Blocks release of GABA, glycine
Monoamine neurotransmitters
Monoamines
Dopamine (DA)
Norepinephrine (NE)/Noradrenaline (NAd)
Epinephrine (Epi)/Adrenaline (Ad)
Serotonin (5-HT)
Melatonin
Histamine
Monoamine Song
Monoamines, do-do do do-do Monoamines, do do do-do Monoamines, do do do do-do do do-do do do-do do do do do-do do
Monoamine Song
Monoamines, do-pa-mine is one Monoamines, norepi, too Monoamines, sero-tonin e-pinephrine, dop-a- mine, nor-epinephrine, melatonin, whoo!
Monoamine Song
Monoamines, mod-u-late neurons Monoamines, throughout the brain Monoamines, keep people happy, brains snappy, not sleepy, not sappy, do-do do-do do-do do
Monoamine neurotransmitters
Monoamines
Dopamine (DA)
Norepinephrine (NE)/Noradrenaline (NAd)
Epinephrine (Epi)/Adrenaline (Ad)
Serotonin (5-HT)
Melatonin
Histamine
Dopamine
Released by two pathways
Substantia nigra -> striatum, meso-striatal projection
Ventral tegmental area (VTA) -> nucleus accumbens, ventral striatum, hippocampus, amygdala, cortex; meso-limbo-cortical projection
DA pathways
DA Disruption linked to
Parkinson’s Disease (mesostriatal)
DA agonists treat (agonists facilitate/increase transmission)
ADHD (mesolimbocortical)
Schizophrenia (mesolimbocortical)
Addiction (mesolimbocortical)
Dopamine receptors
Metabotropic
D1-like (D1 and D5)
more prevalent
D2-like (D2, D3, D4)
target of many antipsychotics
Norepinephrine
Released by
locus coeruleus in pons
postganglionic sympathetic neurons onto target tissues
Role in arousal, mood, eating, sexual behavior
NE and Monoamine oxidase inhibitors (MAOIs)
inactivate monoamines in neurons, astrocytes
MAOIs increase NE, DA
Treatment for depression, but have side effects
NE Anatomy
NE receptors
Metabotropic
α (1,2)
antagonists treat anxiety, panic
β (1,2,3)
‘beta blockers’ in cardiac disease
Serotonin (5-HT)
Released by raphe nuclei in brainstem
Role in mood, sleep, eating, pain, nausea, cognition, memory
Modulates release of other NTs
Most of body’s 5-HT regulates digestion
5-HT anatomy
5-HT receptors
Seven families (5-HT 1-7) with 14 types
All but one metabotropic
5-HT clinical significance
Ecstasy (MDMA) disturbs serotonin
So does LSD
Fluoxetine (Prozac)
Selective Serotonin Reuptake Inhibitor (SSRI)
Inhibits reuptake -> increases extracellular concentration
Treats depression, panic, eating disorders, others
5-HT3 receptor antagonists are anti-mimetics used in treating nausea
Melatonin
Released by pineal gland into bloodstream
Histamine
In brain, released by hypothalamus, projects to whole brain
Metabotropic receptors
Role in arousal/sleep regulation
In body, part of immune response
Other NTs
Gases
Nitric Oxide (NO) , carbon monoxide (CO)
Neuropeptides
Substance P and endorphins (endogenous morphine-like compounds) have role in pain
Orexin/hypocretin , project from lateral hypothalamus across brain, regulate appetite, arousal
Other NTs
Neuropeptides (continued)
Cholecystokinin (CCK) stimulates digestion
Oxytocin and vasopressin released by posterior hypothalamus onto posterior pituitary, regulate social behavior
Non-chemical communication between neurons
Gap junctions
Electrical coupling
Connect cytoplasm directly
Fast, but fixed, hard to modulate
Examples, retina, cardiac muscle
Gap junctions
Ways to think about synaptic communication
Specificity: point-to-point vs. broadcast
Direct vs. modulatory
Agonists vs. antagonists
Agonists vs. Antagonists
Agonists
bind to receptor
mimic action of endogenous chemical
Antagonists
bind to receptor
block/impede action of endogenous chemical
Valium is a GABA-A receptor agonist. This means:
It decreases inhibition
It activates a metabotropic Cl- channel
It facilitates/increases inhibition
It blocks an ionotropic channel
Valium is a GABA-A receptor agonist. This means:
It decreases inhibition
It activates a metabotropic Cl- channel
It facilitates/increases inhibition
It blocks an ionotropic channel
References
Javitt, Daniel C. 2010. “Glutamatergic Theories of Schizophrenia.” Israel Journal of Psychiatry and Related Sciences 47 (1): 4.